1. Technical Field
The present invention relates to a lubricant coating for medical devices, and more particularly, to a hydrophilic polymeric coating which aids medical devices to become slippery when wetted. The lubricant coating of the present invention may be employed to reduce the coefficient of friction of catheters, arterial venous shunts, gastroenteric feed tubes, endotracheal tubes and other medical implants or polymeric substrates. The coating of the present invention also incorporates additive compounds such as anti-microbial that are released in a pharmaceutically acceptable manner. Methods are also provided for the manufacture of the subject lubricant coating and for the application of the same to surfaces of medical devices.
2. Background of the Related Art
Known lubricant coatings applied to surfaces of medical devices include coatings of polyvinylpyrrolidone, polyurethane, acrylic polyester, vinyl resin, fluorocarbons, silicone rubber, and combinations of these substances. For example, Micklus et al., U.S. Pat. Nos. 4,100,309 and 4,119,094, relate to a hydrophilic coating of polyvinylpyrrolidone-polyurethane interpolymer formed using polyisocyanate. Ratner et al., U.S. Pat. No. 3,939,049, relates to a method of grafting hydrogels for lubrication to polymeric substrates using radiation. Hungton et al., U.S. Pat. No. 3,975,350, relates to hydrophilic polyurethane polymers for use as lubricants. Storey. et al. U.S. Pat. No. 3,987,497, relates to a tendon prosthesis having a lubricant hydrogel coating. Many known lubricious coatings are prone to various disadvantages when used in the medical field. Disadvantages of such known lubricants may include insufficiently low coefficient of friction, lack of permanence such as characteristic of silicone or fluorocarbon based coatings, slipperiness when dry as well as wet thus making handling difficult, utilization of hazardous solvents in the manufacture of the same and utilization of unstable reactive materials in the manufacture of the same. Lubricants produced for medical use from unstable reactive material often require the coating solution to be prepared daily or more frequently to be useful and thereby increases waste and expense. Lubricants produced for medical use involving hazardous solvents are undesirable due to patient toxicity concerns and OSHA considerations. Also, lubricant coatings provided for inducing foreign devices into various areas of the body that are susceptible to infection and or thrombogenic reactions have failed to provide a pharmaceutically acceptable carrier for anti-microbial and anti-thrombogenic compounds.
In order to solve these and other potential disadvantages of known lubricants such as those of the above-cited patents incorporated herein by reference, a lubricant coating is needed which when wetted has sufficient lubricity to be useful in the medical device field such as for medical implants and the ability to incorporate within that coating anti-microbial compounds that can be released in a pharmaceutically acceptable manner. The lubricant coating must be capable of adhering to a wide variety of substrates and resist wet abrasion. It would also be desirable to have such a lubricant coating prepared from chemically stable and biocompatible solvents.
The present invention provides a lubricant coating composition comprising a hydrophilic polymer comprising polyvinylpyrrolidone, polyoxyethylene-based isocyanate-terminated prepolymer, ethyl lactate and toluene. The present invention also provides a method of making the subject lubricant coating which adheres to a wide variety of substrates and resists wet abrasion. The subject lubricant coating is chemically stable and is bio-compatible as described in greater detail below.
A method for using the subject lubricant coating composition to coat medical devices is provided herein which involves cleaning or washing, drying, dip coating or applying of the lubricant, air drying or removal of excess lubricant, optionally baking and packaging a medical device either before or after sterilization thereof.
The present invention also provides a medical device whereby at least a portion thereof is coated with the subject lubricant coating which is characterized as being able to achieve a wetted lubricity with a reduction of friction of more than fifty (50) percent.
The present invention also provides a vehicle for incorporating an anti-microbial or anti-thrombogenic agent having pharmaceutically acceptable pharmacokinetic properties without interfering with the lubricous nature of the coating.
The lubricant coating of the present invention has been found particularly useful in lowering the coefficient of friction of medical devices such as indwelling thoracic catheters and other medical devices. The subject coating is manufactured from a blend of one or more C1-12 alkylbenzenes such as, for example, toluene, xylene, or styrene but preferably toluene to increase stability, a C1-12 alkylester of a carboxylic acid such as for example, ethyl lactate, methylbenzoate, or propolyacrylate wherein ethyl lactate is preferred to increase stability, a polymer such as for example polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic acid or polyethylene oxide, but preferably polyvinylpyrrolidone to increase hydrophilicity and lubricity, and an isocyanate-terminated prepolymer such as, for example, polyoxyethylene-based isocyanate such as a toluene or isophorone diisocyanate-based prepolymer such as for example Hypol* PreMA G60 manufactured by Hampshire Corporation, Lexington, Mass., or Vibrathane(copyright) a 4,4-diphenylmethane-disocyanante (MDI) an urethane prepolymer manufactured by Uniroyal, or Pellethane an aromatic ether polyurethane manufactured by Dow Chemical, or Hyrothane manufactured by CardioTech international and or Adiprene(copyright) a low-free TDI manufactured by Uniroyal Chemical.
The urethane increases the binding strength of the coating and controls the rate of release and thus enables the pharmacokinetics of the anti-microbial or other pharmacological additive to be within acceptable pharmaceutical limits and it covalently binds anti-thrombogenic additives to prevent systematic absorption. While different urethanes have different properties and may require different solvent systems, the durometer of the urethane must match the durometer of the medical device to be coated or the functionality of the medical device may become compromised. Solvent selection and blend ration are important to provide adequate solubility and inertness to the hydrophilic urethane and additives. Anti-microbials additives, such as silver salts or antibiotics, may be uniformly suspended within the coating solution. These additives are released on contact with moisture, the rate of release and the lubricious properties of the coating are controlled by altering the ratio of urethane and PVP For further examples of suitable polyisocyanates see Encyclopedia of Polymer Science and Technology, H. F. Mark, N. G. Gaylord and N. M. Bikeles (eds.) (1969) incorporated herein by reference.
Anti-microbial additives utilized within this present invention include the biguanides, especially chlorhexidine and its salts, including chorhexidene acetate, chlorhexideine gluconate, chlorhexidine hydrochloride, and chlorhexidine sulfate, silver and its salts, including silver acetate, silver benzoate, silvercarbonate, silver iodate, silver iodide, silver lactate, silver laurate, silver nitrate, silver oxide, silver palmitate, silver protein, and silver sulfadiazine, polymyxin, tetracycline, aminoglycosides, such as tobramycin and gentamicin, rifampician, bacitracin, neomycin, chloramphenical, miconazole, tolnaftate,quinolone such as oxolinic acid, norfloxacin, nalidix acid, pefloxacin, enoxacin and ciprofloxacin, penicillins such as ampicillin, amoxicillin and piracil, cephalosporins, vancomycin, and combinations of any of the above anti-microbials.
An anti-thrombromgenic additive useful according to this present invention would be heparin. Additionally, organic compounds derived from plants and herbs having desirable pharmacological properties can be utilized. Extracts of plants and herbs have been know to posses anti-microbial activity and their use has been shown to be safe for human and animal consumption. Extracts of such plants, known as phytochemicals, may be utilized for their anti-microbial properties. Some of these extracts, such as grapefruit seed extract, Tea Tree Oil and Myrtle Oil and others can be incorporated into the lubricious coating vehicle and their anti-microbial properties released to the surrounding tissue in an efficacious manner.
In some illustrative embodiments of the present invention colorants, emulsifiers, surfactants, and color stabilizers that are well known within the art are added to the coating formulation. The colorants in the form of dyes or pigments aid in reducing shelf life discoloration or discoloration due to the effects of sterilization. The addition of emulsifiers and surfactants aid in suspension stability of the lubricous coating vehicle and surface wettability. Color stabilizers are sometimes added when the anti-microbial is a silver salt.
The release rate of the pharmacological additive within the lubricious coating and the lubricity of the coating can be controlled by the adjustment of the concentration of the urethane pre-polymer and the concentration of PVP.
The lubricant coating vehicle of the present invention is generally prepared by first obtaining a mixing vat in which to prepare the solution. The mixing vat should be dry and free of water and alcohol. The present lubricant coating vehicle composition is preferably blended at room temperature according to the following component ratios described as follows in weight percent: 1 to 4 weight percent but preferably 1.9 weight percent polyvinylpyrrolidone, 0.5 to 3 weight percent but preferably 1.1 weight percent of the polyoxyethylene-based isocyanate-terminated prepolymer, 15 to 25 weight percent but preferably 18 weight percent alkylester of a carboxylic acid and 60 to 80 weight percent but preferably 79 weight percent toluene. The solution is mixed thoroughly until the polyvinylpyrrotidone and the prepolymer are completely dissolved. The component blending requires approximately one hour. The resulting lubricant coating solution should appear clear to pale yellow. The coating solution is naturally moisture sensitive and will increase in viscosity if not tightly capped during storage. Prior to coating medical devices with the present lubricant coating solution, the particular medical device, such as a catheter, should for best results be cleaned by first filling a container with 100% isopropanol. The medical device is then dip washed in the isopropanol for approximately 5 seconds and dried by forced air at approximately 50 to 90xc2x0 C. to remove surface residual isopropanol and debris. The device should at this point be completely isopropanol free. The medical device is then dip coated for about 5 to 15 seconds in the lubricant coating vehicle solution slowly removed from the solution vat at a rate of about 0.5 inches per second. The catheter or other medical device is then air dried at room temperature for about 10 to 30 seconds to allow any excess lubricant coating solution to drain off. Optionally, excess lubricant may also be removed using absorbent towels. After air drying, the coated medical devices are optionally but preferably baked in forced air ovens at approximately 500 to 60xc2x0+/xe2x88x925xc2x0 for approximately 30 minutes to 3 hours but most preferably for one hour and then removed from the oven. Curing temperature and time are dependent upon the urethane pre-polymer and will vary according to concentrations. During curing, the diisocyanante reacts and becomes part of the polymer structure of the medical device. The medical devices are preferably checked for adequate transparency and to ensure that no solvent smell is present.
In packaging the subject medical devices coated in accordance with the present invention, the devices should not be allowed to touch one another. This is especially true if the environment humidity is high which could cause undesirable moisture absorption by the lubricant coating. To prevent or avoid such contact between the coated medical devices, each device may be packed in either paper, polyethylene tubing or the like depending on the shape of the particular device. If necessary, due to high atmospheric humidity, a desiccant may likewise be necessary in the packaging.
The preferred method of making and using the lubricant coating vehicle of the present invention is described in even greater detail in the following examples which are provided for purposes of further illustration. The following examples as described are not intended to be construed as limiting the scope of the present invention.